Role of Protein Corona in the Fate of Hydrophilic Polymeric Nanoparticles: A Fundamental Study

蛋白电晕在亲水性聚合物纳米颗粒命运中的作用：一项基础研究

• 批准号: 1911478
• 负责人: Shaoyi Jiang
• 金额: $ 40.24万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1911478&HistoricalAwards=false
• 关键词: Role; Protein; Corona; Fate; Hydrophilic

Nanoparticles are particles of matter with dimensions on the order of nanometers. In a biological environment, nanoparticles acquire a layer of proteins, called a corona, and the composition of their corona critically affects the biological fate of nanoparticles. Although a variety of studies have been done to understand the protein corona of nanoparticles over the past decade, little is known about protein corona formed on commonly used hydrophilic (i.e., "water loving") biopolymer nanoparticles. The research team on this project will study the protein corona formed against a number of hydrophilic biopolymers. The objectives are to decode the compositions of the protein coronas and to correlate the identified proteins with the surface chemistry of the nanoparticles. The researchers will then use this knowledge to further understand the biological fate of the nanoparticles. This research will enhance our fundamental understanding of protein corona, identify key proteins responsible for the promotion or reduction of cellular uptake, and guide the design of better and safer nanoparticles for a broad range of applications. The research project serves as a training ground for graduate and undergraduate students to perform cutting edge research. The research team will recruit undergraduate students, particularly students underrepresented in STEM fields, through various on-campus programs. Knowledge from this work will be disseminated through presentations at international conferences, the development of curricula for new courses, and outreach activities. Protein corona on nanoparticles have been shown to be determinant for the biological fate of nanoparticles. At present, most research has focused on corona formation on model hydrophobic polystyrene or inorganic nanoparticle systems. Little is known about protein corona formed on the most commonly used hydrophilic biopolymer nanoparticles. The objectives of this study are to decode the compositions of protein coronas formed against a number of hydrophilic biopolymers using a well-defined, hydrogel nanoparticle system and to correlate the identified proteins with the surface chemistry and fate of nanoparticles. Magnetic nanoparticles will be encapsulated inside the hydrogel nanoparticles to enable the facile harvesting of protein corona using a magnetic field. The compositions of protein coronas will be decoded using state-of-the-art proteomic analysis to provide insights into the interaction of plasma proteins with these hydrophilic polymers. The impact of these adsorbed proteins on the fate of the nanoparticles will be investigated further through cellular uptake experiments using both macrophage and dendritic cells. A fundamental understanding of protein corona will guide the design of better and safer nanoparticles for a wide range of biomedical and engineering applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

纳米颗粒是具有纳米量级尺寸的物质颗粒。 在生物环境中，纳米颗粒获得一层蛋白质，称为冠，其冠的组成严重影响纳米颗粒的生物命运。尽管在过去的十年中已经进行了各种研究来理解纳米颗粒的蛋白质冠，但对在常用的亲水性（即，“亲水”）生物聚合物纳米颗粒。该项目的研究小组将研究针对一些亲水性生物聚合物形成的蛋白质冠。我们的目标是解码蛋白质冠的组成，并将识别的蛋白质与纳米颗粒的表面化学相关联。 然后，研究人员将利用这些知识进一步了解纳米颗粒的生物命运。 这项研究将增强我们对蛋白质冠的基本理解，确定负责促进或减少细胞摄取的关键蛋白质，并指导设计更好，更安全的纳米颗粒，以用于广泛的应用。 该研究项目作为研究生和本科生进行尖端研究的培训基地。 该研究团队将通过各种校园计划招募本科生，特别是在STEM领域代表性不足的学生。将通过在国际会议上介绍情况、为新课程编制课程以及开展外联活动，传播从这项工作中获得的知识。纳米颗粒上的蛋白质冠已被证明是纳米颗粒生物命运的决定因素。目前，大部分研究集中在模型疏水聚苯乙烯或无机纳米粒子体系上的电晕形成。对最常用的亲水性生物聚合物纳米颗粒上形成的蛋白质冠知之甚少。本研究的目的是解码的蛋白质冠形成对一些亲水性生物聚合物使用一个定义明确的，水凝胶纳米颗粒系统的组合物，并与识别的蛋白质与纳米颗粒的表面化学和命运。 磁性纳米颗粒将被封装在水凝胶纳米颗粒内，以使得能够使用磁场容易地收获蛋白质冠。蛋白质冠的组成将解码使用国家的最先进的蛋白质组学分析，以提供深入了解血浆蛋白与这些亲水性聚合物的相互作用。这些吸附的蛋白质对纳米颗粒命运的影响将通过使用巨噬细胞和树突状细胞的细胞摄取实验进一步研究。对蛋白质冠的基本了解将指导设计更好、更安全的纳米颗粒，用于广泛的生物医学和工程应用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的知识进行评估，被认为值得支持影响审查标准。